rs6431393

chr2-235630663-A-Gchr2-235630663-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037131.3(AGAP1):c.164-78516A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,172 control chromosomes in the GnomAD database, including 14,969 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (14969 hom., cov: 33)
• Consequence: AGAP1 NM_001037131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559

Genes affected

AGAP1 (HGNC:16922): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 1) This gene encodes a member of an ADP-ribosylation factor GTPase-activating protein family involved in membrane trafficking and cytoskeleton dynamics. This gene functions as a direct regulator of the adaptor-related protein complex 3 on endosomes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGAP1	NM_001037131.3	c.164-78516A>G		intron_variant		ENST00000304032.13
AGAP1	NM_001244888.2	c.164-78516A>G		intron_variant
AGAP1	NM_014914.5	c.164-78516A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGAP1	ENST00000304032.13	c.164-78516A>G		intron_variant		5	NM_001037131.3

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64610 AN: 152054 Hom.: 14946 Cov.: 33

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.419

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.425 AC: 64683 AN: 152172 Hom.: 14969 Cov.: 33 AF XY: 0.420 AC XY: 31256 AN XY: 74374

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.420

Alfa AF: 0.383 Hom.: 3717

Bravo AF: 0.444

Asia WGS AF: 0.406 AC: 1414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.88
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6431393; hg19: chr2-236539307;